1. Field of the Invention
The present invention relates to a composition and a method for the amelioration and inhibition of bacterial infections, and more particularly, to a composition of a trivalent bismuth salt and dimercaprol. Bacteriocidal and bacteriostatic properties are demonstrated.
2. Description of the Prior Art
Infectious disease of the digestive tract constitute a major health problem throughout the world. Infectious diarrheal disease is one of the leading causes of morbidity and mortality in developing countries. In developed countries, diarrhea and colitis are frequent symptoms during antibiotic therapy. Food contamination with Salmonella, Shigella, Campylobacter, or E. coli poses a major health problem. Diarrhea is the most frequent discomfort among travelers. Even ulcers are now considered an infectious disease.
The finding in 1983 in Helicobacter pylori was the probable cause of ulcers has precipitated intense activity in developing therapies to eradicate this organism from the gastro-intestinal (GI) tract. Effective therapies have emerged, involving combinations of antibiotics, H2-inhibitors and bismuth compounds. These therapies demonstrate an absolute requirement for bismuth to achieve a long-term cure with little probability of reinfection. At present, the preferred form to administer bismuth is as the subcitrate (colloidal bismuth subcitrate or CBS) or as the subsalicylate (BSS, a.k.a. Pepto-Bismol(copyright)).
The mechanisms by which CBS or BSS help to eradicate H. pylori are not fully understood and are currently under investigation. For a review of the properties of CBS, see Wagstaff, et al., Drugs 36:132-157 (1988). Apparently no single mechanism of bismuth activity can account for all of the antiulcer effects suggested in the literature. Indeed a number of therapeutic activities may be involved. Experiments recently performed by Beil et. al., Pharmacology; 47:135-140 (1993) investigated the interactions between colloidal bismuth subcitrate (CBS) and sulfhydryls and their results indicated that DTT did not enhance the antibacterial activity of CBS.
Bismuth compounds are also used in numerous other medical applications. For example, they are used orally as an anti-diarrheal agent, for an upset stomach, nausea, vomiting, and as an internal deodorant, and as skin antiseptics. Bismuth compounds are also used prophylactically for Traveler""s diarrhea, and as an iodoform paraffin paste, they are used to limit infection of surgical wounds. In general, bismuth has antibacterial properties with proven medical usefulness.
Bismuth also has selective effects on expression of virulence factors in bacteria. Concentrations below that which inhibited bacterial growth nevertheless repressed the expression of capsular polysaccharide (CPS) from K. pneumoniae and other members of its family Enterobacteriaciae. It also represses the expression of certain pili involved in adherence. The antibacterial potency of bismith is especially strong under low iron conditions. Increasing iron negates the inhibitory effects of bismuth on bacteria.
Compared to other antimicrobial agents, the potency of bismuth compounds is relatively low, especially when iron is present. In addition, one of the major problems with using bismuth is its insolubility in aqueous solutions.
It is thus an object of the present invention to provide a composition and a method for inhibiting bacterial growth and for preventing bacterial infection. In particular, a composition which includes a trivalent bismuth salt such as BSS, CBS or (Bi(NO3)3 and dimercaprol [2,3-dimercaptopropanol. British and anti-lewisite (BAL)] is provided. When combined, a synergy occurres that enhances the inhibitory action of Bi3+ against bacteria from 100 to 1000-fold. The concentration of both agents can be reduced to nontoxic levels and the combination still possesses powerful bacteriostatic and bactericidal activities against nosocomial pathogens. The composition has broad spectrum bacteriostatic and bacteriocidal effects and therefore is useful as an antibacterial, antiseptic and antimicrobial agent for preventing infection and for disinfecting and cleaning surfaces. It can also be used as a preservative and for killing biofilm organisms and preventing the formation of a biofilm. In particular, the composition of the present invention is useful for treating bacterial infections of the gastro-intestinal (GI) tract. Other agents such as antioxidants, carriers, detergents, antibiotics, preservatives can be used in combination with the composition.
Other features and advantages of the present invention will become apparent from the following description of the invention which refers to the accompanying drawing.